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Mol. Cell. Biol., Jul 1996, 3789-3798, Vol 16, No. 7
Copyright © 1996, American Society for Microbiology

Cyclin A expression is under negative transcriptional control during the cell cycle

X Huet, J Rech, A Plet, A Vie and JM Blanchard
Institut de Genetique Moleculaire de Montpellier, CNRS UMR 5535, France.

Transcription of the gene coding for cyclin A, a protein required for S- phase transit, is cell cycle regulated and is restricted to proliferating cells. To further explore transcriptional regulation linked to cell division cycle control, a genomic clone containing 5' flanking sequences of the murine cyclin A gene was isolated. When it was fused to a luciferase reporter gene, it was shown to function as a proliferation-regulated promoter in NIH 3T3 cells. Transcription of the mouse cyclin A gene is negatively regulated by arrest of cell proliferation. A mutation of a GC-rich sequence conserved between mice and humans is sufficient to relieve transcriptional repression, resulting in a promoter with constitutively high activity. In agreement with this result, in vivo footprinting reveals a protection of the cell cycle-responsive element in G0/early G1 cells which is not observed at later stages of the cell cycle. Moreover, the footprint is present in dimethyl sulfoxide-induced differentiating and not in proliferating Friend erythroleukemia cells. Conversely, two other sites, which in vitro bind ATF-1 and NF-Y, respectively, are constitutively occupied throughout cell cycle progression.


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